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Systemic lupus erythematosus (SLE) is a genetically complex autoimmune disease characterized by loss of immune tolerance to nuclear and cell surface antigens. Previous genome-wide association studies (GWAS) had modest sample sizes, reducing their scope and reliability. Our study comprised 7,219 cases and 15,991 controls of European ancestry, constituting a new GWAS, a meta-analysis with a published GWAS and a replication study. We have mapped 43 susceptibility loci, including ten new associations. Assisted by dense genome coverage, imputation provided evidence for missense variants underpinning associations in eight genes. Other likely causal genes were established by examining associated alleles for cis-acting eQTL effects in a range of ex vivo immune cells. We found an over-representation (n = 16) of transcription factors among SLE susceptibility genes. This finding supports the view that aberrantly regulated gene expression networks in multiple cell types in both the innate and adaptive immune response contribute to the risk of developing SLE.
This article was published in the following journal.
Name: Nature genetics
Treatment multiple tumors by immune therapy can be achieved by mobilizing both innate and adaptive immunity. The programmed death ligand 1 (PD-L1; or CD274, B7-H1) is a critical "don't find me" signal...
Dysregulation of both the innate and the adaptive immune systems has been identified in systemic sclerosis (SSc). However, the mechanisms underlying aberrant immune cell function remain poorly underst...
Both innate and adaptive immune cells are involved in the pathogenesis of nonalcoholic steatohepatitis (NASH), but the crosstalk between innate and adaptive immunity is largely unknown. Here we show t...
Autoimmune and autoinflammatory diseases affect millions worldwide. These classes of disease involve abnormal immune activation of both the innate and adaptive immune systems. While both classes of di...
Immunological memory is an important evolutionary trait that improves host survival upon reinfection. Memory is a characteristic recognized within both the innate and adaptive arms of the immune syste...
The purpose of this study is to determine whether there is a statistical association between the changes from baseline in the levels of two cytokines interleukin (IL)-17A and IL-6 in the s...
Excessive inflammation is associated with tissue damage caused by over-activation of the innate immune system. This can range from mild disease to extreme conditions such as multiple organ...
Gouty diathesis describes uric acid or calcium oxalate nephrolithiasis and low urinary pH (
The aberrant expression of micro-RNAs (miRNAs) has been described in many human diseases, including schizophrenia (SZ). The previous work has indicated a strong genetic association between...
Obesity is driven by genetic and environmental factors. Among the latter, diet is a most important one. The investigators refer to these combinations of genetic and dietary factors as 'gen...
Cytosolic signaling adaptor proteins that were initially discovered by their role in the innate immunity (IMMUNITY, INNATE) response of organisms that lack an adaptive immune system. This class of proteins contains three domains, a C-terminal ligand recognition domain, an N-terminal effector-binding domain, and a centrally located nuclear-binding oligomerization domain. Many members of this class contain a C-terminal leucine rich domain which binds to PEPTIDOGLYCAN on the surface of BACTERIA and plays a role in pathogen resistance.
A DNA-binding protein that represses GENETIC TRANSCRIPTION of target genes by recruiting HISTONE DEACETYLASES. Aberrant Blc-6 expression is associated with certain types of human B-CELL LYMPHOMA.
A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-23 is comprised of a unique 19 kDa subunit and 40 kDa subunit that is shared with INTERLEUKIN-12. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells
An SH2 domain-containing non-receptor tyrosine kinase that regulates signal transduction downstream of a variety of receptors including B-CELL ANTIGEN RECEPTORS. It functions in both INNATE IMMUNITY and ADAPTIVE IMMUNITY and also mediates signaling in CELL ADHESION; OSTEOGENESIS; PLATELET ACTIVATION; and vascular development.
A heterogeneous, immature population of myeloid cells that can suppress the activity of T-CELLS and NATURAL KILLER CELLS in the INNATE IMMUNE RESPONSE and ADAPTIVE IMMUNE RESPONSE. They play important roles in ONCOGENESIS; INFLAMMATION; and INFECTION.
Allergies Automimmune Disease Human Papillomavirus (HPV) Immunology Vaccine Immunology is the study of immunity and the defence mechanisms of the body. A greater understanding of immunology is needed to develop vaccines, understand ...
Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...